Barriers to medication adherence are common in youth with chronic illness and are a source of racial/ethnic disparities in underserved communities. An inherited blood disease, Sickle Cell Disease (SCD) is characterized by chronic and acute illness and reduced quality of life (QOL). It affects African Americans and other underserved communities. Hydroxyurea (HU) is the sole FDA-approved drug therapy for SCD and is highly effective and improves QOL. Poor adherence is common among youth and young adults with SCD. This application, ?Hydroxyurea Adherence for Personal Best in Sickle Cell Treatment: HABIT,? responds to PA-14-029, ?Chronic Condition Self-Management in Children and Adolescents.? The proposed study, a 5-site four-year randomized control trial (RCT), stems directly from our recent R21-funded feasibility study of the same title. Overall goals of reducing barriers to HU use and improving adherence for youth 10-18 years through creation of a daily medication habit. The HABIT feasibility study was delivered to a multi-ethnic sample of parent-youth dyads by culturally aligned community health workers (CHWs), augmented by customized text messaging. The 2-site study demonstrated intervention feasibility and acceptability in a multi-ethnic sample, as well as a sufficient effect on the primary outcomes to power a multi-site efficacy trial. The goal of the proposed multi-site study is to test the efficacy of the HABIT intervention at 6 months and sustainability of the effect at 12 months. The importance of the problem of poor medication adherence, use of CHWs to bridge the gap between health services and underserved parent-youth dyads affected by SCD, the strength of the science, the success of our multi-ethnic feasibility study and the potential application of study findings to youth with other serious chronic illnesses speak to the importance of this trial. Specific Aims: Study aims are to test the efficacy of the HABIT intervention to: Aim 1: Improve daily HU adherence, the primary outcome operationalized two ways: biomarker (approach or exceed a historical Personal best HbF) and pharmacy refill (primary outcome); Aim 2: Improve youth quality of life and self-management responsibility concordance measured by three secondary outcomes: generic and disease-specific QOL and parent/youth concordance regarding delegation of self-management responsibility (secondary outcome); Aim 3: Improve health status measured by two secondary outcomes: acute hospital use (12 month hospital length of stay, admissions and emergency room visits) and self-reported disease symptoms (fatigue, pain interference and intensity); Aim 4: Qualitatively assess impact and sustainability of the intervention on developing a daily medication HU habit from the perspectives of the community health workers (CHWs) and youth-parent-dyads using focus group and individual interviews. If proven efficacious, this approach could be adapted to youth affected by other serious chronic conditions.